The objective of this research program is the evaluation of the dynamic properties of cardiac cell membranes during maturation. Intracellular microelectrode recording techniques will be used to obtain quantitative information about the electrical activity of individual cardiac cells during growth and development of the embryonic chick heart. Critical study of intracellular membrane potentials will be a basis for understanding the regulation of ion transport and the maintenance of cellular homeostasis by cardiac membranes during embryogenesis. This follows from the fact that developmental changes in cellular electrical activity are referable to alterations in transmembrane ion distribution and membrane conductance to ions. Selected pharmacologic agents, known to modify ion transport and membrane potentials in mature hearts, will be used as probes of embryonic heart cell electrical activity at specified times during development. Therefore, alterations in reactivity and responsiveness to drugs will serve as indices of the developmental changes that occur in the drug receptor and in the ionic conductance mechanism (or ionophore) regulated by the drug-receptor interaction. The use of aneural and innervated embryonic hearts will allow an evaluation of the role of the autonomic nervous system in modulating intrinsic cardiac activity as well as membrane reactivity to applied drugs. In addition, the use of organ and cell culture techniques will permit the study of environmental and metabolic factors on receptor properties and distribution during extended time periods in vitro. This study wll provide a better understanding of the pharmacology and physiology of cardiac cells during a critical biologic period. BIBLIOGRAPHIC REFERENCES: Pappano, A. J.: "Development of autonomic neuroeffector transmission in the chick embryo heart" in Developmental and Physiological Correlates of Cardiac Muscle, (ed. by Lieberman, M. and Sano, T.), pp. 235-248, Raven Press, New York, 1975. Pappano, A.J.: "Morphological and functional properties of developing adrenergic neuroeffector junctions in chick embryo heart.", Fed. Proc. (in press), 1976.